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The last decade has witnessed a steady expansion in the number of quantitative trait loci (QTL) mapped for complex phenotypes. However, despite this proliferation, the number of successfully cloned QTL has remained surprisingly low, and to a great extent limited to large effect loci. In this review, we follow the progress of one complex trait locus; a low magnitude moderator of murine emotionality identified some 10 years ago in a simple two-strain intercross, and successively resolved using a variety of crosses and fear-related phenotypes. These experiments have revealed a complex underlying genetic architecture, whereby genetic effects fractionate into several separable QTL with some evidence of phenotype specificity. Ultimately, we describe a method of assessing gene candidacy, and show that given sufficient access to genetic diversity and recombination, progression from QTL to gene can be achieved even for low magnitude genetic effects.

Original publication

DOI

10.1038/sj.ejhg.5201569

Type

Journal article

Journal

Eur J Hum Genet

Publication Date

06/2006

Volume

14

Pages

721 - 728

Keywords

Animals, Behavior, Animal, Crosses, Genetic, Emotions, Mice, Phenotype, Quantitative Trait Loci, Quantitative Trait, Heritable, Recombination, Genetic